# The Chromosome 19 microRNA Cluster Facilitates Cancer Stemness in Hepatocellular Carcinoma

**Authors:** Marian T. Underwood, Varsha Devarapalli, Goodwin G. Jinesh, John H. Lockhart, Marco Napoli, Nino Mtchedlidze, Elsa R. Flores, Andrew S. Brohl

PMC · DOI: 10.3390/ncrna11060074 · Non-Coding RNA · 2025-10-29

## TL;DR

This study shows that overexpression of a microRNA cluster on Chromosome 19 promotes aggressive cancer traits in liver cancer.

## Contribution

The study reveals a novel role of the C19MC microRNA cluster in inducing cancer stemness in hepatocellular carcinoma.

## Key findings

- C19MC overexpression induces cancer stem cell features in hepatocellular carcinoma cells.
- Transcriptomic changes linked to stemness-related genes like NFκB and EMT were observed.
- C19MC is associated with aggressive cancer behavior and poor prognosis in HCC.

## Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the world’s deadliest cancers; however, the mechanisms that contribute to its aggressiveness are poorly understood. In the recent literature, overexpression of the Chromosome 19 MicroRNA Cluster (C19MC) has been associated with an aggressive phenotype and unfavorable prognosis in HCC. However, the molecular consequences of C19MC overexpression in HCC remain poorly understood. Methods: Here, we created a constitutive C19MC-overexpressing HCC model and used two different CRISPR-engineered C19MC-overexpressing HCC models to analyze phenotype and transcriptomic changes. Results: We observed that C19MC overexpression induces cancer stem cell (CSC) phenotypic features in vitro and analyzed transcriptomic changes in genes correlating with stemness, such as NFκB and EMT. Conclusions: C19MC induces changes in HCC that are consistent with stemness and aggression, which provides a better understanding of why C19MC could be a biomarker of poor prognosis.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], ITK (IL2 inducible T cell kinase) [NCBI Gene 3702]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** Cancer (MESH:D009369), HCC (MESH:D006528), aggression (MESH:D010554)
- **Cell lines:** C19MC — Homo sapiens (Human), Primary cutaneous T-cell non-Hodgkin lymphoma, Cancer cell line (CVCL_2633)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12641929/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12641929/full.md

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Source: https://tomesphere.com/paper/PMC12641929